tbuckley/cabot-search huggingface dataset:
Association Between Folic Acid Prescription Fills and Suicide Attempts and Intentional Self-harm Among Privately Insured US Adults
Authors: Robert D. Gibbons, Kwan Hur, Jill E. Lavigne, J. John Mann
Journal: JAMA Psychiatry (2022)

Suicide is a leading cause of death in the United States, having increased more than 30% from 2000 to 2018. An inexpensive, safe, widely available treatment for preventing suicidal behavior could reverse this trend.To confirm a previous signal for decreased risk of suicide attempt following prescription fills for folic acid in a national pharmacoepidemiologic study of patients treated with folic acid.A within-person exposure-only cohort design was used to study the dynamic association between folic acid (vitamin B9) prescription fills over a 24-month period and suicide attempts and intentional self-harm. Data were collected from a pharmacoepidemiologic database of US medical claims (MarketScan) for patients with private health insurance who filled a folic acid prescription between 2012 and 2017. The same analysis was repeated with a control supplement (cyanocobalamin, vitamin B12). Data were analyzed from August 2021 to June 2022.Folic acid prescription fills.Suicide attempt or intentional self-harm resulting in an outpatient visit or inpatient admission as identified by codes from the International Statistical Classification of Diseases, Ninth and Tenth Revisions, Clinical Modification.Data on 866 586 patients were collected; 704 514 (81.30%) were female, and 90 296 (10.42%) were 60 years and older. Overall, there were 261 suicidal events during months covered by a folic acid prescription (5 521 597 person-months) for a rate of 4.73 per 100 000 person-months, compared with 895 suicidal events during months without folic acid (8 432 340) for a rate of 10.61 per 100 000 person-months. Adjusting for age and sex, diagnoses related to suicidal behavior, diagnoses related to folic acid deficiency, folate-reducing medications, history of folate-reducing medications, and history of suicidal events, the hazard ratio (HR) for folic acid for suicide events was 0.56 (95% CI, 0.48-0.65), with similar results for the modal dosage of 1 mg of folic acid per day (HR, 0.57; 95% CI, 0.48-0.69) and women of childbearing age (HR, 0.60; 95% CI, 0.50-0.73). A duration-response analysis (1-mg dosage) revealed a 5% decrease in suicidal events per month of additional treatment (HR, 0.95; 95% CI, 0.93-0.97). The same analysis for the negative control, cyanocobalamin, found no association with suicide attempt (HR, 1.01; 95% CI, 0.80-1.27).This large-scale pharmacoepidemiologic study of folic acid found a beneficial association in terms of lower rates of suicide attempts. The results warrant the conduct of a randomized clinical trial with suicidal ideation and behavior as outcomes of interest. If confirmed, folic acid may be a safe, inexpensive, and widely available treatment for suicidal ideation and behavior.
Broadly neutralizing antibodies to SARS-related viruses can be readily induced in rhesus macaques
Authors: Wan-ting He, Meng Yuan, Sean Callaghan, Rami Musharrafieh, Ge Song, Murillo Silva, Nathan Beutler, Wen-Hsin Lee, Peter Yong, Jonathan L. Torres, Mariane Melo, Panpan Zhou, Fangzhu Zhao, Xueyong Zhu, Linghang Peng, Deli Huang, Fabio Anzanello, James Ricketts, Mara Parren, Elijah Garcia, Melissa Ferguson, William Rinaldi, Stephen A. Rawlings, David Nemazee, Davey M. Smith, Bryan Briney, Yana Safonova, Thomas F. Rogers, Jennifer M. Dan, Zeli Zhang, Daniela Weiskopf, Alessandro Sette, Shane Crotty, Darrell J. Irvine, Andrew B. Ward, Ian A. Wilson, Dennis R. Burton, Raiees Andrabi
Journal: Science Translational Medicine (2022)

To prepare for future coronavirus (CoV) pandemics, it is desirable to generate vaccines capable of eliciting broadly neutralizing antibody responses to CoVs. Here, we show that immunization of macaques with SARS-CoV-2 spike (S) protein with a two-shot protocol generated potent serum receptor binding domain cross-neutralizing antibody responses to both SARS-CoV-2 and SARS-CoV-1. Furthermore, responses were equally effective against most SARS-CoV-2 variants of concern (VOCs) and some were highly effective against Omicron. This result contrasts with human infection or many two-shot vaccination protocols where responses were typically more SARS-CoV-2 specific and where VOCs were less well neutralized. Structural studies showed that cloned macaque neutralizing antibodies, particularly using a given heavy chain germline gene, recognized a relatively conserved region proximal to the angiotensin converting enzyme 2 receptor binding site (RBS), whereas many frequently elicited human neutralizing antibodies targeted more variable epitopes overlapping the RBS. B cell repertoire differences between humans and macaques appeared to influence the vaccine response. The macaque neutralizing antibodies identified a pan-SARS-related virus epitope region less well targeted by human antibodies that could be exploited in rational vaccine design.
Disparities in Physician Compensation—A Call to Action
Authors: Kathryn T. Chen, Junko Ozao-Choy, Christian de Virgilio
Journal: JAMA Surgery (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
Comparison of Work Relative Value Units for Outpatient Pediatric and Adult Dermatology Encounters
Authors: Krittin J. Supapannachart, Zachary Wolner, Allison E. Miller, Jeanette R. Comstock, Mengyu Di, Leslie P. Lawley, Beth A. Drolet, Lauren A. V. Orenstein
Journal: JAMA Dermatology (2022)

Dermatologists with specialty training in pediatric dermatology are scarce, which can mean extended wait times and reduced access to care for patients. Lower compensation for pediatric dermatology visits compared with adult visits may affect physician career choice and contribute to workforce shortages.To evaluate differences in work relative value units (wRVUs) generated by pediatric and adult outpatient dermatology encounters.This cross-sectional study used data from outpatient dermatology encounters at a single-site academic center in Atlanta, Georgia, from September 1, 2016, to March 31, 2020. Encounters with patients younger than 18 years were classified as pediatric, and encounters with those 18 years or older were classified as adult. Encounters with missing data were excluded as were those generating 0 wRVUs, inpatient visits, nursing visits, postoperative encounters, cosmetic procedures, phototherapy visits, and Mohs surgery encounters.Work relative value units generated per encounter type were assessed through multivariable linear regression models adjusted for the potential confounder of sex.The study included 12 989 pediatric dermatology encounters (mean [SD] age, 7.3 [5.2] years; 7586 [58.4%] girls) and 78 057 adult dermatology encounters (mean [SD] age, 54.9 [18.9] years; 45 724 [58.6%] women). Pediatric encounters were associated with 0.23 (95% CI, 0.21-0.25; P < .001) fewer wRVUs than adult encounters after adjusting for sex. In a mediation analysis, biopsies and destruction of premalignant lesions explained 74.1% (95% CI, 69.6%-77.9%; P < .001) of the wRVU difference between pediatric and adult encounters.This cross-sectional study found significant differences in wRVUs generated between adult and pediatric dermatology encounters that were largely attributable to biopsies and destruction of premalignant lesions. Policies that increase the value of cognitive services to be on par with procedural care may mitigate wRVU differences and improve reimbursement for pediatric dermatologists.
Differences in Skin Cancer Rates by Transplanted Organ Type and Patient Age After Organ Transplant in White Patients
Authors: Lee Wheless, Nimay Anand, Allison Hanlon, Mary-Margaret Chren
Journal: JAMA Dermatology (2022)

Although it is known that patients with thoracic organ transplants develop skin cancer more frequently than those who receive nonthoracic organ transplants, patterns of risk for subsequent skin cancers are unknown.To further characterize organ transplant recipients who develop multiple skin cancers and assess for patterns of development of additional skin cancers beyond the first skin cancer diagnosis by patient age and transplanted organ type.This cohort study used validated electronic health record-based data from a single tertiary care academic medical center to identify 5129 solid organ transplant recipients who underwent transplant surgery between 1992 and 2017 and were older than 18 years at the time of transplant. The cohort was limited to White patients because they have the highest skin cancer risk based on phenotype. The mean follow-up was 6.6 years. Data were analyzed June 9, 2021, to May 31, 2022.Differences in rates of skin cancer development for first and subsequent skin cancers were measured using t test or analysis of variance and χ2 tests for continuous and categorical variables. Rates of skin cancer development were compared based on organ type and patient age at transplant using Fine-Gray tests and cumulative incidence plots.A total of 5129 organ transplant recipients (mean [SD] age, 51.3 [12.9] years; 3287 men [64.1%]) were included. Of these, 695 patients (13.6%) had development of at least 1 skin cancer, with 6842 skin cancers identified in the cohort overall. Compared with liver transplant recipients, heart, lung, or kidney recipients were more likely to develop at least 1 skin cancer (χ2 test, 25.6; df, 4; P < .001). There was no significant difference by transplanted organ type in the rate of developing a second or third skin cancer; however, the age at transplant was associated with the time to developing a second (χ2 test, 20.4; df, 4; P < .001) or third (χ2 test, 10.9; df, 4; P < .02) skin cancer.This cohort study found that there was no difference by organ type for development of subsequent skin cancers in organ transplant recipients, and recipients of all organ types developed additional skin cancers at high rates after the initial skin cancer.
Sustained Aurora Kinase B Expression Confers Resistance to PI3K Inhibition in Head and Neck Squamous Cell Carcinoma
Authors: Pooja A. Shah, Vaishnavi Sambandam, Anne M. Fernandez, Hongyun Zhao, Tuhina Mazumdar, Li Shen, Qi Wang, Kazi M. Ahmed, Soma Ghosh, Mitchell J. Frederick, Jing Wang, Faye M. Johnson
Journal: Cancer Research (2022)

Abstract Tumor suppressor mutations in head and neck squamous cell carcinoma (HNSCC) dominate the genomic landscape, hindering the development of effective targeted therapies. Truncating and missense mutations in NOTCH1 are frequent in HNSCC, and inhibition of PI3K can selectively target NOTCH1 mutant (NOTCH1MUT) HNSCC cells. In this study, we identify several proteins that are differentially regulated in HNSCC cells after PI3K inhibition based on NOTCH1MUT status. Expression of Aurora kinase B (Aurora B), AKT, and PDK1 following PI3K inhibition was significantly lower in NOTCH1MUT cell lines than in wild-type NOTCH1 (NOTCH1WT) cells or NOTCH1MUT cells with acquired resistance to PI3K inhibition. Combined inhibition of PI3K and Aurora B was synergistic, enhancing apoptosis in vitro and leading to durable tumor regression in vivo. Overexpression of Aurora B in NOTCH1MUT HNSCC cells led to resistance to PI3K inhibition, while Aurora B knockdown increased sensitivity of NOTCH1WT cells. In addition, overexpression of Aurora B in NOTCH1MUT HNSCC cells increased total protein levels of AKT and PDK1. AKT depletion in NOTCH1WT cells and overexpression in NOTCH1MUT cells similarly altered sensitivity to PI3K inhibition, and manipulation of AKT levels affected PDK1 but not Aurora B levels. These data define a novel pathway in which Aurora B upregulates AKT that subsequently increases PDK1 selectively in NOTCH1MUT cells to mediate HNSCC survival in response to PI3K inhibition. These findings may lead to an effective therapeutic approach for HNSCC with NOTCH1MUT while sparing normal cells. Significance: Aurora B signaling facilitates resistance to PI3K inhibition in head and neck squamous cell carcinoma, suggesting that combined inhibition of PI3K and Aurora kinase is a rational therapeutic strategy to overcome resistance.
Reply: Questioning the existence of Aif1 +, Csf1r + mesenchymal stem cells
Authors: Chen Zong, Yan Meng, Lixin Wei
Journal: Hepatology (2022)

1 Tumor Immunology and Gene Therapy Center Third Affiliated Hospital of Second Military Medical UniversityShanghaiChina 2National Center for Liver CancerShanghaiChina *Correspondence Lixin Wei, Tumor Immunology and Gene Therapy Center, Third Affiliated Hospital of Second Military Medical University, 225 Changhai Road, Shanghai 200438, China. Email: [email protected]
Measured Blood Pressure, Genetically Predicted Blood Pressure, and Cardiovascular Disease Risk in the UK Biobank
Authors: So Mi Jemma Cho, Satoshi Koyama, Yunfeng Ruan, Kim Lannery, Megan Wong, Ezimamaka Ajufo, Hokyou Lee, Amit V. Khera, Michael C. Honigberg, Pradeep Natarajan
Journal: JAMA Cardiology (2022)

Hypertension remains the major cardiovascular disease risk factor globally, but variability in measured blood pressure may result in suboptimal management. Whether genetic contributors to elevated blood pressure may complementarily inform cardiovascular disease risk assessment is unknown.
Reevaluating Corticosteroid Classification Models in Patient Patch Testing
Authors: Joyce Y. Chen, James A. Yiannias, Matthew R. Hall, Molly J. Youssef, Lisa A. Drage, Mark D. P. Davis, Yul W. Yang
Journal: JAMA Dermatology (2022)

Individuals with allergic contact dermatitis to one topical corticosteroid may also react to other corticosteroids. Corticosteroid classification models have been proposed to predict such copositivity, recommend representative screening corticosteroids, and guide allergen avoidance.To use patient data to determine copositivity patterns between corticosteroids and evaluate against previous corticosteroid classification models.This qualitative study included a retrospective analysis of the Mayo Clinic Contact Dermatitis Group corticosteroid patch test data from 2010 to 2019. Among patients undergoing patch testing with the Mayo Clinic's standard or steroid series who consented to research participation, 5637 patients were included in the analysis. Copositivity rates were determined between corticosteroids and analyzed by hierarchical clustering for comparison to previous classification models.The frequency of patch test positivity to each of the analyzed corticosteroids was noted and compared with previously published patch test positivity rates. Copositivity rates between each pair of corticosteroids were determined, and overall copositivity patterns were analyzed and evaluated against known steroid classes.A total of 49 472 individual patches were applied to 5637 patients, testing 18 corticosteroids. Patch test positivity rates ranged between 0.3% and 4.7%. The fluocinonide positivity rate corresponded to the highest copositivity rate with other corticosteroids (mean [SD], 50.7% [26.1%]). Tixocortol-21-pivalate, 0.1%, and tixocortol-21-pivalate, 1%, positivity rates corresponded to the lowest copositivity rates (mean [SD], 4.1% [1.7%] and 3.6% [1.4%], respectively). Hierarchical clustering elucidated patterns that did not support previous corticosteroid classification models.In this qualitative study, copositivity rates were variable between corticosteroids, and overall patch test positivity for allergy to topical corticosteroids was rare. Previously published corticosteroid classifications are not supported by real patient-derived data and may not be accurate in predicting corticosteroid copositivity.
The Smart(est) Choice for Dual Antiplatelet Therapy Is a Patient-Directed One
Authors: Ajay J. Kirtane, Roxana Mehran
Journal: JAMA Cardiology (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Cardiology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Cardiology journal
Modeling Preclinical Cancer Studies under Physioxia to Enhance Clinical Translation
Authors: Adedeji K. Adebayo, Harikrishna Nakshatri
Journal: Cancer Research (2022)

Abstract Oxygen (O2) plays a key role in cellular homeostasis. O2 levels are tightly regulated in vivo such that each tissue receives an optimal amount to maintain physiologic status. Physiologic O2 levels in various organs range between 2% and 9% in vivo, with the highest levels of 9% in the kidneys and the lowest of 0.5% in parts of the brain. This physiologic range of O2 tensions is disrupted in pathologic conditions such as cancer, where it can reach as low as 0.5%. Regardless of the state, O2 tension in vivo is maintained at significantly lower levels than ambient O2, which is approximately 21%. Yet, routine in vitro cellular manipulations are carried out in ambient air, regardless of whether or not they are eventually transferred to hypoxic conditions for subsequent studies. Even brief exposure of hematopoietic stem cells to ambient air can cause detrimental effects through a mechanism termed extraphysiologic oxygen shock/stress (EPHOSS), leading to reduced engraftment capabilities. Here, we provide an overview of the effects of ambient air exposure on stem and non-stem cell subtypes, with a focus on recent findings that reveal the impact of EPHOSS on cancer cells.
Self‐Assembled Corrole/Chitosan Photothermal Nanoparticles for Accelerating Infected Diabetic Wound Healing
Authors: Yunhao Yu, Rui Tian, Yu Zhao, Xudong Qin, Liefeng Hu, Jun‐Jie Zou, Ying‐Wei Yang, Jian Tian
Journal: Advanced Healthcare Materials (2022)

Microvascular dysfunction caused by hyperglycemia leads to slow healing of diabetic wounds and significantly increases the risk of bacterial infection. The misuse of antibiotics can also lead to bacterial resistance, making the management of diabetic wounds more challenging. Thus, developing new antibacterial agents or strategies to overcome antibiotic resistance is highly pursued. Herein, novel supramolecular photothermal nanoparticles (MCC/CS NPs), assembled from mono-carboxyl corrole (MCC) and chitosan via hydrogen bonding and π-π stacking, are developed and used for treating bacterial wound infection. The MCC molecules possess good photothermal performance and the chitosan with inherent bioactivity can exert moderate antibacterial effects. The aggregation of MCC in MCC/CS NPs induced by chitosan-templated self-assembly further quenches molecular fluorescence and realizes an extraordinary photothermal conversion efficiency of 66.4%. Moreover, the highly positively charged MCC/CS NPs can selectively target bacteria via electrostatic interactions. Under near-infrared laser irradiation, the MCC/CS NPs achieve potent photothermal and inherent antimicrobial synergistic effects against Escherichia coli and methicillin-resistant Staphylococcus aureus (MRSA) in vitro. Furthermore, the bacteria-infected diabetic wound model confirms that the MCC/CS NPs can effectively kill drug-resistant bacteria, accelerate wound healing and angiogenesis, and show good biocompatibility, representing a novel and efficient photothermal antibacterial nanoplatform.